Selection and use of umbilical cord cell fractions suitable for transplantation
Inventors
Peled, Tony • COHEN, Einat Galamidi • Snyder, David
Assignees
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Publication Number
US-11746325-B2
Publication Date
2023-09-05
Expiration Date
Abstract
Methods of selecting umbilical cord blood units for ex-vivo expansion, separation of CD133+/CD34+ positive and uncultured CD133+/CD34+ negative fractions, methods for expanding the selected CD133+/CD34+ fraction, selection of expanded populations of CD133+/CD34+ cord blood cells for transplantation to subjects in need thereof and the therapeutic use of suitable selected, ex-vivo expanded CD133+/CD34+ and unselected CD133/CD34 negative cord blood fractions for transplantation in the clinical setting, for treatment of hematological malignancies are provided. The present invention also envisions kits comprising the expanded and unselected cord blood fractions.
Core Innovation
The invention relates to a method of treating a hematological disease in a subject in need thereof by using a single umbilical cord blood unit suitable for transplantation. The method separates the single umbilical cord blood unit into a first selected blood cell fraction comprising CD133+/CD34+ selected cells and a second unselected blood cell fraction comprising CD133/CD34 negative cells. The approach treats the hematological disease by combining these two fractions after subsequent processing and transplantation.
The CD133+/CD34+ selected fraction is ex vivo cultured under conditions allowing for cell proliferation. The culture conditions include providing nutrients and serum and a combination of cytokines including stem cell factor, thrombopoietin, FLt3 ligand, and IL-6 together with nicotinamide in an amount between 1.0 mM to 10 mM.
The method cryopreserves the ex-vivo cultured first CD133+/CD34+ selected blood cell fraction and the uncultured second unselected blood cell fraction. The method then includes thawing the cryopreserved cultured and uncultured fractions and transplanting the thawed ex-vivo cultured first selected fraction together with the thawed uncultured second unselected fraction into the subject. The method thereby treats the hematological disease in the subject.
Claims Coverage
The independent claim is directed to treating a hematological disease by separating a single umbilical cord blood unit into CD133+/CD34+ selected cells and CD133/CD34 negative cells, ex vivo culturing the CD133+/CD34+ fraction with specific cytokines plus nicotinamide (1.0 mM to 10 mM), cryopreserving both fractions, thawing both fractions, and transplanting both into the subject. Dependent claims further refine selection/performance outcomes and administration constraints, including pre-cryopreservation suitability criteria, nicotinamide sub-ranges, infection and engraftment-related outcomes, and infusion solution handling.
Separating a single umbilical cord blood unit into selected and unselected fractions
The method separates a single umbilical cord blood unit suitable for transplantation into (i) a first, selected blood cell fraction comprising CD133+/CD34+ selected cells and (ii) a second, unselected blood cell fraction comprising CD133/CD34 negative cells.
Ex vivo culturing the CD133+/CD34+ selected fraction with cytokines and nicotinamide
The method ex vivo cultures the first blood cell fraction comprising CD133+/CD34+ selected cells under conditions allowing for cell proliferation, including providing nutrients, serum and a combination of cytokines including each of stem cell factor, thrombopoietin, FLt3 ligand and IL-6 and nicotinamide in an amount between 1.0 mM to 10 mM.
Cryopreserving both the cultured selected fraction and the uncultured unselected fraction
The method cryopreserves the ex-vivo cultured first, CD133+/CD34+ selected blood cell fraction and the uncultured second, unselected blood cell fraction from step (b).
Thawing and transplanting both thawed fractions into the subject
The method includes thawing the ex-vivo cultured first selected and uncultured second, unselected blood cell fractions and transplanting the thawed ex-vivo cultured first selected and uncultured second unselected blood cell fractions into a subject in need thereof.
Overall, the claim coverage centers on the paired use of a CD133+/CD34+ selected fraction that is ex vivo cultured with a defined cytokine/nicotinamide combination and an uncultured CD133/CD34-negative unselected fraction, with both fractions cryopreserved, thawed, and transplanted together to treat a hematological disease.
Stated Advantages
Decreases time from transplantation to platelet engraftment compared to transplanting one or two units of unmanipulated cord blood.
Decreases the risk of grade 2/3 bacterial or invasive fungal infections by 100 days post-transplant compared to one or two units of unmanipulated cord blood.
Documented Applications
Treating a hematological disease in a subject in need thereof using transplantation of thawed ex-vivo cultured CD133+/CD34+ selected cells together with thawed uncultured CD133/CD34 negative unselected cells from a single umbilical cord blood unit.
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